创伤性脑水肿是重型颅脑损伤患者早期死亡的重要原因，而小胶质细胞是参与颅脑炎症反应最主要的免疫细胞，但脑创伤后全身性炎症反应介导的小胶质细胞活化在脑水肿形成中的作用尚不清楚。课题组前期研究发现：重型颅脑损伤大鼠于伤后行脾切除能够显著降低脑组织水肿程度，提高大鼠生存率，由此推测：脑外伤后脾源性炎症反应促进了脑创伤区域小胶质细胞的活化，加重了继发性脑水肿的形成。本课题拟以大鼠小胶质细胞作为研究对象，通过体外培养及建立脑创伤动物模型，采用激光共聚焦、荧光定量PCR、EMSA等分子生物学技术，观察脾源性炎症反应对小胶质细胞分泌炎性细胞因子、吞噬及抗原提呈等方面的影响，证实脾源性炎症反应可以直接激活小胶质细胞；在此基础上，从信号转导机制着手，阐明炎症主要信号通路MAPK-NFκB在小胶质细胞活化过程中的调节作用。研究结果将深化对创伤性脑水肿发病机制的认识，为重型颅脑创伤患者控制脑水肿提供新的治疗策略。

Traumatic brain edema is a major cause of early death in patients with severe traumatic brain injury,and the role of microglia, the main immune cells involved in the inflammatory response of brain, whose activation mediated by systemic inflammatory response in brain edema formation after traumatic brain injury remains unclear. Our preliminary study suggests that rats underwent splenectomy after severe traumatic brain injury could significantly reduce brain edema and improve survival rate. Therefore,we hypothesize that spleen-derived systemic inflammation response after traumatic brain injury promotes microglial activation in traumatic region and exacerbates secondary brain edema. The intention of this project is to investigate the role of microglia in inflammatory cytokines secreting, phagocytosis and antigen presenting in spleen-derived inflammatory response through in vitro and in vivo experiment using confocal, fluorescence quantitative PCR， EMSA and other molecular biological techniques to confirm the spleen-derived inflammatory response, which could directly activate microglia. Based on this basis, we are going to elucidate the regulation of the main inflammatory signaling pathways of MAPK-NFκB in microglia activation process starting from signal transduction mechanisms. Findings gained from this study will deepen our understanding on the pathogenesis of traumatic brain edema and provide new treatment strategies for patients with severe traumatic brain injury.